A unique disease known as amyotrophic lateral sclerosis (ALS) and Parkinsonism Dementia Complex (PDC) or ALS/PDC is observed in the Chamorro people of Guam. The clinical features of ALS observed are similar if not identical to ALS observed in other parts of the world. However, Guam ALS is neuropathologically unique in that neurofibrillary tangles, are observed in the cortex and spinal cord, a finding atypical of classical ALS. PDC is Parkinsonism features observed with dementia, again, the neuropathologic features, which are essentially identical to Guam ALS, distinguish PDC from Parkinson's disease. Guam ALS and PDC are considered different clinical. The goal of this proposal is to identify the genetic susceptibility factors involved in ALS/PDC. To accomplish this goal, the mode of inheritance of ALS/PDC will be examined in 1st degree relatives of a case-control Registry established in 1958-1963. Analysis of segregation patterns should provide information to generate a genetic model of ALS/PDC. Since environmental factors, possibly unique to Gum, also probably play a role in susceptibility, environmental risk factors will be incorporated into the genetic model. To actually identify genetic factors, linkage analysis of ALS/PDC pedigrees will be performed to map the susceptibility gene(s). If needed, non-parametric methods will be used for mapping loci. Results from genetic modeling will be used to design the analysis methods.